Total elbow arthroplasty (TEA) is not as predictable or durable as joint arthroplasties for the knee and hip. Unfortunately, other treatments for arthritis and complex trauma of the elbow are even less effective. Little attention has been paid to TEA failure, despite the devastating disability that accompanies the problem. Possible reasons for failure include biomechanical, patient, and surgical factors. But efforts to explain which factors are most detrimental are hampered by the lack of data on the loads across the elbow during routine daily activities, making it difficult to assess the relative importance of these factors. Nonetheless, the most prevalent failure modes, aseptic loosening and excessive polyethylene wear, suggest that biomechanical factors dominate. We propose, therefore, to answer the following question: How do biomechanical, patient, and surgical factors affect implant performance in total elbow arthroplasty? To answer this question, we will use an integrated approach to accomplish three specific aims. First, we will combine motion analysis of TEA patients performing common activities with a computational model to calculate the joint contact loads. Next, we will apply these loads to numerical models of the humerus and ulna implanted with TEA components to examine the stresses created in the cement and bone, at the interfaces, and at the polyethylene joint surfaces as measures of potential implant loosening. In performing these analyses, we will utilize statistically-based methods to examine important environmental variables (joint loads, component position and orientation, and bone anatomy and materials properties) in a timely and cost efficient manner. Finally, we will confirm the mechanical failure modes from our analyses using radiographic observations from a retrospective series of failed TEA cases together with retrieval analysis of the removed implant components. We can then decipher which factors are important in generating loads and interface conditions that explain why failures occur in particular areas within the bone-implant system. We will also explain which factors most affect bearing surface failure by comparing our analytical results with observations of wear and deformation on retrieved polyethylene components. The information provided from our study may, in turn, allow us to better predict impending failures in patients who have already undergone TEA, suggest alterations in surgical technique and instrumentation to improve outcomes, and suggest postoperative limits in activity that TEA patients should consider. As likely, however, given the poor performance of contemporary TEAs, we will also discover design alterations that will improve performance. PUBLIC HEALTH RELEVANCE: Total elbow replacement is not as predictable or durable as joint replacements for the knee and hip, yet failures of total elbow replacements failed elbow arthroplasty are usually catastrophic, resulting in a flail arm that severely disable the entire upper limb. We aim to explain biomechanical, patient, and surgical factors that affect the performance of elbow replacements. Our goal is to explain the locations and mechanisms of failure, thereby suggesting solutions to improve the efficacy of this treatment.